Ignite Creation Date:
2024-05-05 @ 12:04 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00235690
Status:
COMPLETED
Last Update Posted:
2015-12-17
First Post:
2005-10-06
Brief Title:
Optimizing Dosing of Colistin for Infections Resistant to All Other Antibiotics Approved NIH Protocol Dated 120607DMID Protocol 07-0036
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
Pharmacokinetics and Pharmacodynamics of Intravenous Colistin- Pilot Study
Status:
COMPLETED
Status Verified Date:
2015-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
More than 80 patients at the University of Pittsburgh Medical Center have been infected with Pseudomonas aeruginosa lacking susceptibility to all commercially available antibiotics except colistin This antibiotic was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time Dosing recommendations on the basis of these pharmacokinetic studies are listed in the drugs product information However there are no dosing recommendations for patients requiring renal replacement therapy either intermittent hemodialysis or continuous venovenous hemofiltration Furthermore the science of antibiotic dosing pharmacodynamics has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal Furthermore even though physicians refer to colistin administration the only intravenous form of the drug is colistin methanesulfonate CMS CMS is converted in the body to colistin Both CMS and colistin have different pharmacokinetic and antimicrobial activities For this reason we the investigators at the University of Pittsburgh are performing a pilot study of the pharmacokinetics of intravenous CMScolistin in patients requiring this antibiotic for clinical purposes Plasma concentrations will be determined around a CMScolistin dose once the drug has reached steady state Concentrations in pulmonary epithelial lining fluid will also be determined in patients with pneumonia Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations The measurement of CMS and colistin levels will be determined by a laboratory in Australia which developed these assays A submission is being made to the National Institutes of Health NIH for funding of a multicenter study which will address this research question with a greater sample size The study proposed here is a pilot study in order to prove the feasibility of the research approach and to provide preliminary data for the NIH proposal
Detailed Description:
At baseline upon signing informed consent the following information will be collected Demographic data - age sex height weight state of birth underlying illnesses underlying infection immunosuppression antibiotic use laboratory results current medication use any other prior medical problemshistory and clinical outcomes
The research coordinator will contact the patient on days 14 28 and 90 days after the infection to determine clinical outcome If the patient is still an inpatient the research coordinator will visit the patient in their hospital room to evaluate the patients health status This visit will take about 10 minutes If the patient has been discharged from the hospital the patient will be contacted by telephone by the research coordinator to determine the health status if no recent electronic medical record exists This telephone contact will take about 10 minutes
Blood work and microbiologic samples to be collected
Collection of six samples of 3 mL blood on the third or fourth day of colistin therapy will occur These samples will be collected
immediately pre-dose
at the end of the colistin infusion
30 minutes after the end of the colistin infusion
60 minutes after the end of the colistin infusion
4 hours after the end of the colistin infusion
12 hours after the end of the colistin infusion or immediately prior to the next dose if the drug is being given every 12 hours
Indwelling venous and arterial access lines if already in place will be utilized for the pharmacological studys blood draws
Rationale The samples will be utilized for quantification of plasma levels of colistin
Collection of microbiologic samples within 48-96 hours of the initiation of colistin therapy These samples are two sets of blood cultures if the patient had bacteremia a mini-BAL for quantitative bacterial culture if the patient had pneumonia and a cerebrospinal fluid collection if the patient had Gram negative meningitis and has a cerebrospinal fluid drain in situ Additionally these samples will be used to determine the concentrations of colistin and CMS at the site of infection A 3mL blood sample will be taken at the same time as these specimen collections to determine concomitant serum concentrations of colistin and CMS
Rationale These samples will be used to determine if there has been rapid bacteriologic clearance of infection and to determine the concentrations of drug at the site of infection
The blood samples will be processed and stored in a -80 C freezer in a secured laboratory under the supervision of the principal investigator These samples will then be sent to the laboratory of Drs Jian Li and Roger Nation in Melbourne Australia to determine the amount of colistin and CMS that reached the participants blood following dose administration All samples will be sent de-identified
All samples will be analyzed to obtain the amount of colistin and CMS found in the blood The biologic samples will be under the control of the principal investigator of this research project To protect confidentiality all personal identifiers ie name social security number and birth date will be removed de-identified and replaced with a specific code number The information linking these code numbers to the corresponding subjects identities will be kept in a separate secure location The investigators on this study will keep the samples indefinitely All samples sent outside of the UPMC facility will be de-identified If a subject withdraws and provides the request in writing samples collected and not already processed will be destroyed All samples at UPMC will be kept in the investigators laboratory located in Scaife Hall Room 812 3550 Terrace Street All patients will be seen at the UPMC facility while they are inpatients
Other items to be collected for study purposes
Microbiology - the organism that caused the infection will be sub-cultured in the clinical microbiology laboratory after the diagnosis has been obtained since the microbiology lab would otherwise destroy the culture and provided to the investigators All subsequent Gram negative bacterial isolates will be sub-cultured and stored for similar purposes
An unopened vial of colistin from the same batch as used for the patient will be collected for analysis so the actual dose of colistin can be calculated
The research coordinator will contact the patient on days 14 28 and 90 days after the infection to determine clinical outcome If the patient is still an inpatient the research coordinator will visit the patient in their hospital room to evaluate the patients health status This visit will take about 10 minutes If the patient has been discharged from the hospital the patient will be contacted by telephone by the research coordinator to determine the health status if no recent electronic medical record exists This telephone contact will take about 10 minutes
Blood work and microbiologic samples to be collected
Collection of six samples of 3 mL blood on the third or fourth day of colistin therapy will occur These samples will be collected
immediately pre-dose
at the end of the colistin infusion
30 minutes after the end of the colistin infusion
60 minutes after the end of the colistin infusion
4 hours after the end of the colistin infusion
12 hours after the end of the colistin infusion or immediately prior to the next dose if the drug is being given every 12 hours
Indwelling venous and arterial access lines if already in place will be utilized for the pharmacological studys blood draws
Rationale The samples will be utilized for quantification of plasma levels of colistin
Collection of microbiologic samples within 48-96 hours of the initiation of colistin therapy These samples are two sets of blood cultures if the patient had bacteremia a mini-BAL for quantitative bacterial culture if the patient had pneumonia and a cerebrospinal fluid collection if the patient had Gram negative meningitis and has a cerebrospinal fluid drain in situ Additionally these samples will be used to determine the concentrations of colistin and CMS at the site of infection A 3mL blood sample will be taken at the same time as these specimen collections to determine concomitant serum concentrations of colistin and CMS
Rationale These samples will be used to determine if there has been rapid bacteriologic clearance of infection and to determine the concentrations of drug at the site of infection
The blood samples will be processed and stored in a -80 C freezer in a secured laboratory under the supervision of the principal investigator These samples will then be sent to the laboratory of Drs Jian Li and Roger Nation in Melbourne Australia to determine the amount of colistin and CMS that reached the participants blood following dose administration All samples will be sent de-identified
All samples will be analyzed to obtain the amount of colistin and CMS found in the blood The biologic samples will be under the control of the principal investigator of this research project To protect confidentiality all personal identifiers ie name social security number and birth date will be removed de-identified and replaced with a specific code number The information linking these code numbers to the corresponding subjects identities will be kept in a separate secure location The investigators on this study will keep the samples indefinitely All samples sent outside of the UPMC facility will be de-identified If a subject withdraws and provides the request in writing samples collected and not already processed will be destroyed All samples at UPMC will be kept in the investigators laboratory located in Scaife Hall Room 812 3550 Terrace Street All patients will be seen at the UPMC facility while they are inpatients
Other items to be collected for study purposes
Microbiology - the organism that caused the infection will be sub-cultured in the clinical microbiology laboratory after the diagnosis has been obtained since the microbiology lab would otherwise destroy the culture and provided to the investigators All subsequent Gram negative bacterial isolates will be sub-cultured and stored for similar purposes
An unopened vial of colistin from the same batch as used for the patient will be collected for analysis so the actual dose of colistin can be calculated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NIH | None | None | None |